RNAi-mediated knockdown of Notch-1 leads to cell growth inhibition and enhanced chemosensitivity in human breast cancer

Ji,

doi:10.3892/or_00000712

Cited by 31 publications

(8 citation statements)

References 18 publications

(22 reference statements)

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“…Crosstalk with signalling molecules such as Ras and Wnt also mediate the role of Notch in breast cancer cell proliferation, with studies detecting concomitant suppression of these pathways in response to Notch inhibition (Mittal et al, 2014;Lai et al, 2018). (Mungamuri et al, 2006;Osipo et al, 2008a;Efferson et al, 2010;Zang et al, 2010;Zhu et al, 2013;Li L. et al, 2014b;Hossain et al, 2018). Our lab have shown that Notch also stimulates Akt through a secreted factor, which triggers stabilisation of p53 through ASK1/JNK signalling (Meurette et al, 2009).…”

Section: Cell Proliferationmentioning

confidence: 80%

Notch Signalling in Breast Development and Cancer

Edwards

Brennan

2021

Front. Cell Dev. Biol.

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The Notch signalling pathway is a highly conserved developmental signalling pathway, with vital roles in determining cell fate during embryonic development and tissue homeostasis. Aberrant Notch signalling has been implicated in many disease pathologies, including cancer. In this review, we will outline the mechanism and regulation of the Notch signalling pathway. We will also outline the role Notch signalling plays in normal mammary gland development and how Notch signalling is implicated in breast cancer tumorigenesis and progression. We will cover how Notch signalling controls several different hallmarks of cancer within epithelial cells with sections focussed on its roles in proliferation, apoptosis, invasion, and metastasis. We will provide evidence for Notch signalling in the breast cancer stem cell phenotype, which also has implications for therapy resistance and disease relapse in breast cancer patients. Finally, we will summarise the developments in therapeutic targeting of Notch signalling, and the pros and cons of this approach for the treatment of breast cancer.

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Section: Cell Proliferationmentioning

confidence: 80%

Notch Signalling in Breast Development and Cancer

Edwards

Brennan

2021

Front. Cell Dev. Biol.

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“…Notch signaling controls vascular development, bone physiology and vascular development in the marrow, and is aberrant in several cancers [56][57][58][59][60] . Guo and colleagues reported that Notch1 overexpression in MM cells increases Vegf-a production and tumor vascular density in vivo 61 .…”

Section: Discussionmentioning

confidence: 99%

Osteocyte Vegf-a contributes to myeloma-associated angiogenesis and is regulated by Fgf23

Mulcrone

Edwards

Petrusca

et al. 2020

Sci Rep

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Multiple Myeloma (MM) induces bone destruction, decreases bone formation, and increases marrow angiogenesis in patients. We reported that osteocytes (Ocys) directly interact with MM cells to increase tumor growth and expression of Ocy-derived factors that promote bone resorption and suppress bone formation. However, the contribution of Ocys to enhanced marrow vascularization in MM is unclear. Since the MM microenvironment is hypoxic, we assessed if hypoxia and/or interactions with MM cells increases pro-angiogenic signaling in Ocys. Hypoxia and/or co-culture with MM cells significantly increased Vegf-a expression in MLOA5-Ocys, and conditioned media (CM) from MLOA5s or MM-MLOA5 co-cultured in hypoxia, significantly increased endothelial tube length compared to normoxic CM. Further, Vegf-a knockdown in MLOA5s or primary Ocys co-cultured with MM cells or neutralizing Vegf-a in MM-Ocy co-culture CM completely blocked the increased endothelial activity. Importantly, Vegf-a-expressing Ocy numbers were significantly increased in MM-injected mouse bones, positively correlating with tumor vessel area. Finally, we demonstrate that direct contact with MM cells increases Ocy Fgf23, which enhanced Vegf-a expression in Ocys. Fgf23 deletion in Ocys blocked these changes. These results suggest hypoxia and MM cells induce a pro-angiogenic phenotype in Ocys via Fgf23 and Vegf-a signaling, which can promote MM-induced marrow vascularization.

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“…35 Suppression of Notch1 inhibited cell growth and improved drug sensitivity of breast cancer. 33 The combined effect of miR and Notch1 in RB had been published, but the interaction between miR-515-5p and Notch1 in RB was studied for the first time. Thereafter, functional rescue experiments were conducted, which indicated that overexpressing Notch1 attenuated the inhibitory effect of miR-515-5p on RB cell proliferation and the promotion of drug sensitivity.…”

Section: Discussionmentioning

confidence: 99%

“…Notch1 was reported to involve in the malignant phenotype of RB 12,31 and chemosensitivity of multiple tumors. [32][33][34][35][36] The results of RT-qPCR and Western blot showed that Notch1 was significantly upregulated in RB cells (p < 0.05) ( Figure 1A and B). However, the upstream miR regulating Notch1 expression remained unclear.…”

Section: Notch1 Was Upregulated In Rb Cells and Mir-515-5p Inhibited mentioning

confidence: 99%

<p>Effect of miR-515-5p on Proliferation and Drug Sensitivity of Retinoblastoma Cells</p>

Yuan¹,

Yan²,

Tong³

2020

CMAR

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Background: Retinoblastoma (RB) is a common malignancy in children eyes. Aberrant microRNA (miR) expression is observed in many cancer cases. miR-515-5p is reported to be concerned with the course of many cancers. This study explores the role of miR-515-5p in proliferation and drug sensitivity of RB cells. Methods: Human RB cell lines (WERI-RB1, SO-RB50 and Y79) and human retinal pigment epithelial cell line ARPE-19 were utilized in this study. Drug-resistant cells SO-RB50/VCR and SO-RB50/CBP were constructed for the following experiments. The expressions of miR-515-5p and Notch1 in RB cells were detected. Notch1 was significantly upregulated in RB cells while miR-515-5p was notably downregulated. Then, the binding relationship between miR-515-5p and Notch1 was predicted and verified. Results: miR-515-5p negatively regulated Notch1 expression. In vitro and in vivo experiments revealed that overexpressed miR-515-5p inhibited RB cell proliferation and enhanced drug sensitivity. Functional rescue experiment suggested that miR-515-5p regulated RB cell proliferation and drug sensitivity via inhibiting Notch1 expression. Conclusion: It could be concluded that overexpressed miR-515-5p suppressed proliferation and drug resistance of RB cells by targeting Notch1 expression, indicating that miR-515-5p might constitute a promising therapy target for RB.

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RNAi-mediated knockdown of Notch-1 leads to cell growth inhibition and enhanced chemosensitivity in human breast cancer

Cited by 31 publications

References 18 publications

Notch Signalling in Breast Development and Cancer

Notch Signalling in Breast Development and Cancer

Osteocyte Vegf-a contributes to myeloma-associated angiogenesis and is regulated by Fgf23

<p>Effect of miR-515-5p on Proliferation and Drug Sensitivity of Retinoblastoma Cells</p>

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